Substituted N-(β-alkoxy-ethyl)-N-(4-phenoxy-benzyl)-dichloro-acetamides and process for their preparation

Abstract

Substituted N-( beta -Alkoxy-Ethyl)-N-(4-Phenoxy Benzyl)-Dichoroacetamides are provided for the chemotherapeutic treatment of amebiasis.

We claim: 
     
       1. A compound of the formula ##STR37## wherein R is C 1  -C 6  alkyl; Y is (a) ##STR38##  wherein R' is hydrogen or C 1  -C 6  alkyl, and   R 1  is   (1) C 1  -C 12  alkyl   (a') unsubstituted or   (b') substituted by one or more substituents selected from the group consisting of (1) halogen, (2) carboxy, (3) carbamoyl, (4) methylthio, (5) --OR', wherein R' is hydrogen or C 1  -C 6  alkyl, (6) ##STR39##  wherein R' and R" are independently hydrogen or C 1  -C 6  alkyl and (7) phenyl, which is unsubstituted or substituted by one or more hydroxy groups; or   (2) phenyl,   (a') unsubstituted or   (b') substituted by one or more substituents selected from the group consisting of (1') halogen, (2'), C 1  -C 6  alkyl, (3') trihalo-C 1  -C 6  --alkyl, (4') nitro, (5')--OR' wherein R' is   hydrogen or C 1  -C 6  and (6') ##STR40##  wherein R' and R" are independently hydrogen or C 1  -C 6  alkyl or a pharmaceutically or veterinarily acceptable salt thereof.   
     
     
       2. A compound of the formula ##STR41## wherein R is C 1  -C 3  alkyl; Y is ##STR42##  wherein R 1  is (a') C 1  -C 6  alkyl unsubstituted or substituted by one or more substituents selected from the group consisting of halogen, methylthio, carboxy, carbamoyl, unsubstituted phenyl, hydroxy, amino and phenyl; or a pharmaceutically or veterinarily acceptable salt thereof.   
     
     
       3. A compound selected from the group-consisting of: N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-acetamido)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-chloroacetamido)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-dichloroacetamido)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-trifluoroacetamido)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-propionyiamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-pyvaloylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-benzoylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-glycinylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-norvalinylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-alanylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-valinylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-leucinylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-β-alanylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-γ-amino-butyrylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-lysinylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-serinylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-methionylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-tyrosinylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-aspartylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-asparagylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-glutamylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-glutaminylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-lactoylamino)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-hydroxy-acetamido)-benzyl]-dichloroacetamide;   N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-α-hydroxy-butyrylamino)-benzyl]-dichloroacetamide; or the pharmaceutically or veterinarily acceptable salt thereof.     
     
     
       4. A pharmaceutical composition suitable for the treatment of amebiasis, comprising a therapeutically effective amount of a compound of any one of claims 1, 2, or 3 and a pharmaceutically acceptable carrier. 
     
     
       5. Method of treating a patient suffering from amebiasis, said method comprising administering to said patient a therapeutically effective amount of a compound of any one of claims 1, 2 or 3. 
     
     
       6. The compound N-(β-ethoxy-ethyl)-N-[4-phenoxy-(4'-acetamido)-benzyl]-dichloroacetamide. 
     
     
       7. A pharmaceutical composition suitable for the treatment of amebiasis, comprising a therapeutically effective amount of the compound of claim 6, and a pharmaceutically acceptable carrier. 
     
     
       8. Method of treating a patient suffering from amebiasis, said method comprising administering to said patient a therapeutically effective amount of the compound of claim 6.